The focus of my career in patient-oriented research (POR) has been to study how interactions between HIV- 1 and key cells involved in innate and adaptive immunity influence control of HIV-1replication and disease progression. The ultimate goal of these studies is to apply knowledge gained in the laboratory toward the development of more effective immune-based therapies that control HIV-1 replication and/or more fully restore immune function. The novel work outlined in this K24 proposal involves patient oriented laboratory- based studies that bridge the gap between innate and adaptive immunity by 1) determining the role that dendritic cells (DCs)play in initiating and perpetuating HIV-associated chronic immune activation and 2) evaluating factors that influence dendritic cell survival in the setting of HIV-1infection. These studies are critical to an understanding of HIV-1pathogenesis, in particular in understanding how HIV-1initiates and perpetuates the destructive cycle of chronic immune activation and T cell dysfunction. The University of Colorado Health Sciences Center and National Jewish Medical Research Center provide a rich and supportive environment in which to carry out this research as well as to train junior investigators. My own positive experiences with excellent mentors who invested in my career development have instilled a desire in me to nurture the careers of junior investigators dedicated to a career in patient-oriented HIV-1 research. Throughout my career I have had the opportunity to serve as primary research mentor to numerous intelligent, enthusiastic pre-doctoral and post-doctoraltrainees. The purpose of this mid-career investigator award in POR is to facilitate this important research in the field of applied HIV-1immunology while also allowing me to dedicate myself more fully to mentoring activities. The receipt of this K24 award would provide me with protected time to better support the independent career development of trainees and to help them establish a niche in the research community. It would also provide necessary funding for supplies, technical support, and travel to ensure the successful implementation of trainee research.